| Objective:To observe the clinical efficacy of Yiqi Juanbi decoction in the treatment of osteoarthritic synovitis of the knee and to investigate the specific mechanism of action and targets of Yiqi Juanbi decoction in interfering with fibroblast-like synovial cells of the human knee from the cellular level,to provide a scientific basis and new ideas for the conservative treatment of osteoarthritic synovitis of the knee.Methods:1.Clinical study: 70 patients with osteoarthritic synovitis of the knee with spleen loss and healthy movement who attended the Rheumatology and Bone Disease Centre of Gansu Provincial Hospital from January 2022 to December 2022 and met the criteria were randomly divided into a test group and a control group,and the control group was given Celecoxib capsules orally based on conventional treatment,while the test group was given Yiqi Juanbi decoction orally based on conventional treatment.The total duration of treatment was three weeks.The patients’ TCM symptoms score,VAS score,WOMAC score,and knee swelling degree score were evaluated before and after treatment,and the data were statistically analyzed using SPSS26.0 to conclude.2.Experimental validation: The drug-containing serum of Yiqi Juanbi decoction was prepared,and the isolated human knee synovial fibroblasts were divided into five groups(blank serum control group,model group,low drug-containing serum group,medium drugcontaining serum group,and high drug-containing serum group),and CCK8 observed the cell proliferation after the lipopolysaccharide-induced inflammatory cell model;ELISA detected the levels of IL-17 and TNF-α;the WB method was used to detect The molecular mechanism of action and the targets of action of Yiqi Juanbi decoction in the treatment of knee synovitis were initially explored.Results:1.Clinical study(1)The total symptom scores of patients in both groups were significantly reduced after treatment compared with those before treatment(P<0.01),and the reduction of total symptom scores in the test group was better than that in the control group(P<0.001).In the control group,the scores of swollen joints,painful joints,poor joint movement,and weakness decreased compared to those before treatment(P<0.05),but the scores of abdominal distension,loose stools,and thinness did not change significantly(P>0.05);the scores of all symptoms in the test group decreased significantly after treatment compared to those before treatment(P<0.01).Comparison of the symptom scores between the two groups after treatment showed that the test group had better improvement than the control group in the scores of symptoms of joint swelling,joint pain,abdominal distension and dullness,loose stools,yellowing of the face and weakness(P<0.01);the improvement in the scores of symptoms of unfavorable joint movement was comparable between the two groups(P>0.05).(2)The total effective rate after treatment was 93.75% and 83.33% in the test group and the control group,respectively,and the total effective rate in the test group was significantly better than that in the control group(P<0.001).(3)The VAS scores,WOMAC scores,and joint swelling scores of patients in both groups were significantly lower after treatment compared with those before treatment(P<0.01),and the level of reduction in the test group was greater than that in the control group(P<0.05).(4)During the study,no significant adverse effects were observed except for one patient in the control group who withdrew from the study due to worsening symptoms and opted for surgery.2.Cellular experiments(1)The CCK8 results showed that the cell survival rate of the model group increased significantly compared with that of the blank serum control group(P<0.001);compared with the model group,the survival rate of FLS cells was significantly reduced in all the drugcontaining serum groups of Yiqi Juanbi decoction(P<0.001),and the survival rate of FLS cells in the group with a high concentration of Yiqi Juanbi decoction was the lowest,suggesting that the drug-containing serum of Yiqi Juanbi decoction could inhibit FLS cell proliferation in a concentration-dependent manner cell proliferation.(2)The ELISA results showed that the levels of TNF-α and IL-17 protein were significantly increased in the model group compared with the blank control group(P<0.001);compared with the model group,the concentration-dependent reduction of TNF-α protein in the supernatant of Yiqi Juanbi decoction containing serum was observed(P<0.001);the medium and high dose groups of Yiqi Juanbi decoction containing serum could significantly inhibit the expression level of IL-17 protein(P<0.05),while there was no significant difference in the expression of IL-17 protein in the low-dose group(P>0.05).(3)The WB test results showed that the expression of IL-1β and MMP13 protein in the model group was significantly higher compared with the blank control group(P<0.001);compared with the model group,the expression of IL-1β and MMP13 protein in the synovial cells was significantly reduced in all concentration groups of Yiqi Juanbi decoction containing serum(P<0.05).Conclusion:(1)The clinical study showed that the clinical efficacy of Yiqi Juanbi decoction in treating knee osteoarthritis synovitis patients with spleen disorders is better than that of the Celecoxib capsule,especially in improving the accompanying symptoms such as abdominal distension and dullness,loose stools,and yellow skin in patients.No significant adverse effects were observed during the treatment period.(2)Cellular experiments showed that Yiqi Juanbi decoction might inhibit synovial cell proliferation and the expression of IL-17,TNF-α,IL-1β,and MMP13 to exert its intervention effect on synovial cells in the knee joint. |